Cystic Fibrosis With Pulmonary Manifestations Clinical Trial
Official title:
Combined Dry Powder Tobramycin and Nebulized Colistin Inhalation in CF Patients
To assess whether the inhalative combination of Tobramycin/Colistin is more effective in reducing Pseudomonas colony forming units (CFUs) and improvement of lung function than Colistin in mono-therapy.
Cystic fibrosis (CF), the most common autosomal recessive disorder in Western countries, is
caused by mutations of the cystic fibrosis transmembrane conductance regulator molecule
(CFTR) and affects approximately 40.000 patients in Europe. The majority of CF patients
develop chronic pulmonary infections with Pseudomonas aeruginosa. These are normally treated
with single antibiotics, administered orally, intravenously or inhalatively. Once the
infection becomes chronic, eradication of the pathogen is not any more possible due to
biofilm formation of the pathogen and increasing resistance. However, inhalative antibiotic
combination therapy might be more efficient than single antibiotic therapy in chronically
infected CF patients. This notion is supported by previous in vitro and animal studies using
Tobramycin/Colistin combination therapy. Importantly, a pilot study in five CF patients who
inhaled consecutively Colistin and Tobramycin solutions for 4 week, revealed a decrease of
log10 2.52 ± 2.5 cfu of P. aeruginosa in sputum specimens during the course of the treatment
compared to baseline values (p=0.027). The treatment was shown to be safe and well tolerated.
However, forced expiratory volume in 1 sec (FEV1) did not differ significantly.
Taking advantage of the new development of dry powder inhalation (DPI) antibiotics,
specifically TOBI© Podhaler, a larger randomised trial has been performed in which the
combined TOBI© Podhaler and Colistin treatment is compared to the monotherapy with Colistin.
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